JAK inhibitors match standard immunosuppressants in systemic sclerosis — but come with caveats. A new international registry study found that patients with systemic sclerosis (SSc) treated with JAK inhibitors had similar outcomes to those on standard therapies like mycophenolate mofetil or rituximab, but faced a high discontinuation rate and significant adverse events including infections and malignancies.
A new retrospective study using data from the European Scleroderma Trials and Research (EUSTAR) group registry offers one of the first real-world looks at JAK inhibitors in systemic sclerosis (SSc) — and the picture is mixed. Across 36 patients treated with baricitinib, tofacitinib, or upadacitinib, outcomes for lung function (FVC) and skin thickening (mRSS) were broadly comparable to those seen with standard immunosuppressants like mycophenolate mofetil, rituximab, and methotrexate.
However, the safety profile raised flags. Nearly a third of patients permanently stopped JAK inhibitor therapy — mostly due to treatment failure — and adverse events included infections, lab abnormalities, three malignancies, and one fatal sepsis case. Drug retention dropped to just 43% by 36 months.
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Why it matters: SSc is a rare, difficult-to-treat autoimmune disease with limited therapeutic options. While these findings are exploratory and limited by small sample size, they offer early signals that JAK inhibitors may benefit certain SSc subgroups — particularly those with diffuse disease or an inflammatory phenotype — while underscoring the need for careful monitoring of cancer and infection risk.
